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Endoscopic innovations to increase the adenoma detection rate during colonoscopy

World Journal of Gastroenterology 2014年第9期20卷 2200-2211页

作者： vincent k dik Leon MG Moons Peter D Siersema Department of Gastroenterology and Hepatology University Medical Center Utrecht 3508 GA Utrecht the Netherlands

Up to a quarter of polyps and adenomas are missed during colonoscopy due to poor visualization behind folds and the inner curves of flexures, and the presence of flat lesions that are difficult to detect. These numbers may however be conservative because they mainly come from back-to-back studies performed with standard colonoscopes, which are unable to visualize the entire mucosal surface. In the past several years, new endoscopic techniques have been introduced to improve the detection of polyps and adenomas. The introduction of high definition colonoscopes and visual image enhancement technologies have been suggested to lead to better recognition of flat and small lesions, but the absolute increase in diagnostic yield seems limited. Cap assisted colonoscopy and water-exchange colonoscopy are methods to facilitate cecal intubation and increase patients comfort, but show only a marginal or no benefit on polyp and adenoma detection. Retroflexion is routinely used in the rectum for the inspection of the dentate line, but withdrawal in retroflexion in the colon is in general not recommended due to the risk of perforation. In contrast, colonoscopy with the Third-Eye Retroscope® may result in considerable lower miss rates compared to standard colonoscopy, but this technique is not practical in case of polypectomy and is more time consuming. The recently introduced Full Spectrum Endoscopy™ colonoscopes maintains the technical capabilities of standard colonoscopes and provides a much wider view of 330 degrees compared to the 170 degrees with standard colonoscopes. Remarkable lower adenoma miss rates with this new technique were recently demonstrated in the first randomized study. Nonetheless, more studies are required to determine the exact additional diagnostic yield in clinical practice. Optimizing the efficacy of colorectal cancer screening and surveillance requires high definition colonoscopes with improved virtual chromoendoscopy technology

关键词： Colonoscopy Endoscopic innovations Adenoma detection Polyp detection Gastrointestinal endoscopy

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FE65:a hub for neurodevelopment

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Neural Regeneration Research 2024年第9期19卷 1883-1884页

作者： Yuqi Zhai Laura Lok-Haang Ng Dennis dik-Long Chau kwok-Fai Lau School of Life Sciences Faculty of ScienceThe Chinese University of Hong KongHong Kong Special Administrative RegionChina

FE65,initially identified as a binding partner of amyloid precursor protein(APP),is an adaptor protein enriched in the brain and regulated during ***65 belongs to the FE65 protein *** family is comprised of three memb... 详细信息

关键词： family development partner

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The roles of atypical protein kinase Cs(aPkCs) in the nervous system: targets for neuroregeneration?

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Neural Regeneration Research 2020年第8期15卷 1475-1476页

作者： Dennis dik-Long Chau kwok-Fai Lau School of Life Sciences The Chinese University of Hong Kong

The protein kinase C(PkC)family:PkC family is a subgroup of the AGC serine-threonine kinases that consists of 10 distinct members in mammals(Spitaler and Cantrell,2004).They all contain a C-terminal catalytic domain that is connected to the N-terminal regulatory *** are subdivided into three classes according to their structures and *** classical/conventional PkC isoforms possess tandem C1 domains that bind to their well-known activators diacylglycerol and phorbol esters and also contain a C2 domain that mediates the binding of Ca^2+-sensitive anionic phospholipids.

关键词： domains. subgroup system

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Aurone derivatives as Vps34 inhibitors that modulate autophagy

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Acta Pharmaceutica Sinica B 2019年第3期9卷 537-544页

作者： Guodong Li Joshua William Boyle Chung-Nga ko Wu Zeng vincent kam Wai Wong Jian-Bo Wan Philip Wai Hong Chan dik-Lung Ma Chung-Hang Leung State key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao999078China School of Chemistry Monash UniversityClayton3800Australia Department of Chemistry Hong Kong Baptist UniversityHong Kong999077China State key Laboratory of Quality Research in Chinese Medicine Macao University of Science and TechnologyMacao999078China Department of Chemistry University of WarwickCoventry CV47ALUK

We report in this study the identification of a natural product-like antagonist(1a) of Vps34 as a potent autophagy modulator via structure-based virtual screening. Aurone derivative 1a strongly inhibited Vps34 activity in cell-free and cell-based assays. Significantly, 1a prevents autophagy in human cells induced either by starvation or by an mT OR inhibitor. In silico modeling and kinetic data revealed that 1a could function as an ATP-competitive inhibitor of Vps34. Moreover, it suppressed autophagy in vivo and without inducing heart or liver damage in mice. 1a could be utilized as a new motif for more selective and efficacious antagonists of Vps34 for the potential treatment of autophagy-related human diseases.

关键词： Autophagy Natural products Vps34 Inhibitor Structure-based virtual screening Vesicle trafficking Heart or liver damage Aurone derivative

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Special Topic:DNA-Based Biosensors

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Journal of Analysis and Testing 2022年第1期6卷 1-2页

作者： Jue-Wen Liu dik-Lung Ma Department of Chemistry University of WaterlooWaterlooON N2L 3G1Canada Department of Chemistry Hong Kong Baptist UniversityKowloon TongHong Kong 999077China

While the function of DNA in biology is for storage of genetic information,chemists have developed methods to obtain DNA sequences with catalytic and molecular recognition ***,DNA is a highly attractive molecule for developing *** probes are known for their detection of complementary DNA and *** addition,DNA aptamers allow for the detection of,essentially,any type of *** coupling DNA with biological elements such as CRISPR-Cas12,highly sensitive detection with signal amplification can also be ***,using DNA as a sensor component and as a target are hot areas of research for biomedical diagnosis,environmental monitoring,and food safety.

关键词： diagnosis attractive complementary

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Group 8–9 Metal‑Based Luminescent Chemosensors for Protein Biomarker Detection

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Journal of Analysis and Testing 2018年第1期2卷 77-89页

作者： dik‐Lung Ma Chun Wu Guodong Li Chung‐Hang Leung Department of Chemistry Faculty of ScienceHong Kong Baptist UniversityKowloon TongHong KongChina State key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacaoChina

The development of transition metal complex-based luminescent chemosensors has recently aroused increasing interest for protein biomarker labelling and detection,especially for the real-time diagnosis and treatment of *** is owing to their unique photophysical properties,particularly their long-lived and environmentally sensitive emission,which can be easily controlled via the structural modification of *** this overview,we highlight recent examples of protein biomarker detection using group 8–9 metal-based luminescent chemosensors,including the frequently employed ruthenium(II)and iridium(III)*** mechanisms and sensing modes are described and compared,and the outlook and future directions of this field are discussed as well.

关键词： Chemosensor Biomarker Metal complex Luminescence

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Discovery of a tetrahydroisoquinoline-based CDk9-cyclin T1 proteineprotein interaction inhibitor as an anti-proliferative and anti-migration agent against triple-negative breast cancer cells

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Genes & Diseases 2022年第6期9卷 1674-1688页

作者： Shasha Cheng Guan-Jun Yang Wanhe Wang dik-Lung Ma Chung-Hang Leung State key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoTaipaMacao SARPR China Department of Chemistry Hong Kong Baptist UniversityKowloon TongHong Kong SARPR China Institute of Medical Research Northwestern Polytechnical UniversityXi’anShaanxi 710072PR China Department of Biomedical Sciences Faculty of Health SciencesUniversity of MacaoMacao SARPR China

Triple-negative breast cancer(TNBC)is a highly aggressive and metastasizing cancer that has the worst prognosis out of all breast cancer *** epithelial emesenchymal transition(EMT)and cancer stem cells(CSCs)have been proposed as important mechanisms underlying TNBC ***9 is highly expressed in breast cancer,including TNBC,where it promotes EMT and induces cancer cell *** this study,we have identified a tetrahydroisoquinoline derivative(compound 1)as a potent and selective CDk9-cyclin T1 inhibitor via virtual ***,by targeting the ATP binding site,compound 1 not only inhibited CDk9 activity but also disrupted the CDk9-cyclin T1 proteineprotein interaction(PPI).Mechanistically,compound 1 reversed EMT and reduced the ratio of CSCs by blocking the CDk9-cyclin T1 interaction,leading to reduced TNBC cell proliferation and *** date,compound 1 is the first reported tetrahydroisoquinoline-based CDk9-cyclin T1 ATP-competitive inhibitor that also interferes with the interaction between CDk9 and cyclin *** 1 may serve as a promising scaffold for developing more selective and potent anti-TNBC *** work also provides insight into the role of the CDk9-cyclin T1 PPI on EMT and CSCs and highlights the feasibility and significance of targeting CDk9 for the treatment of TNBC.

关键词： Cancer stem cells CDk9-cyclin T1 Epithelial mesenchymal transition Proteineprotein interaction(PPI) Triple-negative breast cancer(TNBC)

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Inhibition of the CDk9-cyclin T1 protein-protein interaction as a new approach against triple-negative breast cancer

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1390-1405页

作者： Sha-Sha Cheng Yuan-Qing Qu Jia Wu Guan-Jun Yang Hao Liu Wanhe Wang Qi Huang Feng Chen Guodong Li Chun-Yuen Wong vincent kam Wai Wong dik-Lung Ma Chung-Hang Leung Institute of Chinese Medical Sciences and State key Laboratory of Quality Research in Chinese Medicine University of MacaoMacao 999078China Dr.Neher’s Biophysics Laboratory for Innovative Drug Discovery State Key Laboratory of Quality Research in Chinese MedicineMacao University of Science and TechnologyMacao 999078China State key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products Ningbo UniversityKow loon TongHong Kong 999077China Laboratory of Biochemistry and Molecular Biology School of Marine SciencesNingbo UniversityNingbo 315211China Department of Chemistry Hong Kong Baptist UniversityNingbo 315211China Institute of Medical Research Northwestern Polytechnical UniversityXi'an 710072China Department of Chemistry City University of Hong KongHong Kong 999077China Department of Biomedical Sciences Faculty of Health SciencesUniversity of MacaoMacao 999078China

Cyclin-dependent kinase 9(CDk9) activity is correlated with worse outcomes of triplenegative breast cancer(TNBC) patients. The heterodimer between CDk9 with cyclin T1 is essential for maintaining the active state of the kinase and targeting this protein-protein interaction(PPI) may offer promising avenues for selective CDk9 inhibition. Herein, we designed and generated a library of metal complexes bearing the 7-chloro-2-phenylquinoline CN ligand and tested their activity against the CDk9cyclin T1 PPI. Complex 1 bound to CDk9 via an enthalpically-driven binding mode, leading to disruption of the CDk9-cyclin T1 interaction in vitro and in cellulo. Importantly, complex 1 showed promising anti-metastatic activity against TNBC allografts in mice and was comparably active compared to cisplatin. To our knowledge, 1 is the first CDk9-cyclin T1 PPI inhibitor with anti-metastatic activity against TNBC. Complex 1 could serve as a new platform for the future design of more efficacious kinase inhibitors against cancer, including TNBC.

关键词： Metal complex kinase inhibitor Protein-protein interaction Epigenetics Triple-negative breast cancer Metastasis

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Development of an orally bioavailable selective inhibitor of the menin-MLL

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Genes & Diseases 2023年第5期10卷 1735-1738页

作者： Hai-Jing Zhong Wanhe Wang Wei Zhou Jia-Xin Liang Yung-Chi Cheng dik-Lung Ma Chung-Hang Leung State key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SARChina Department of Chemistry Hong Kong Baptist UniversityKowloon TongHong Kong SARChina Department of Pharmacology Yale University School of MedicineNew HavenCT 06520USA Department of Biomedical Sciences Faculty of Health SciencesUniversity of MacaoMacao SARChina International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE) College of PharmacyJinan UniversityGuangzhouGuangdong 510632China

The protein–protein interaction between menin and mixed lineage leukemia(MLL)plays an important role in the development of human hepatocellular carcinogenesis(HCC)and is associated with poor prognosis of HCC patients.1,2 Hence,interrupting the menin-MLL interaction is an attractive strategy in cancer treatment,particularly for liver cancer.3,4 In this study,we identified complex C1 as the first rhodium(III)-based orally bioavailable selective inhibitor of the menin-MLL interaction for HCC.

关键词： MLL prognosis carcinogenesis

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Pharmacophore modeling for the identification of small-molecule inhibitors of TACE

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中国药理学与毒理学杂志 2015年第S1期29卷 95-96页

作者： Li-juanLIU ka-HoLEUNG ShengLIN DanielShiu-HinCHAN DewiSUSANTI Wei-dongRAO PhilipWaiHongCHAN dik-LungMA Chung-HangLEUNG State key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macao Macao China Department of Chemistry Hong kong Baptist University Hongkong China Division of Chemistry and Biological Chemistry School of Physical and Mathematical Sciences Nanyang Technological University Singapore 637371 Singapore School of Chemistry Monash University Ciayton 3800 Victoria Australiate

OBJECTIVE To employ pharmacophore modeling to identify a TACE inhibitor from an inhouse database of 66 organic *** To identify the common features required for TACE inhibition,we generated a pharmacophore model from a set of TACE-selective inhibitor using the Common Feature Pharmacophore Model protocol implemented in Discovery Studio 3.1.1.A fluorimetric assay was used to investigate the potential ability of compounds to inhibit TACE enzymatic *** ability of compound 1 to inhibit TACE activity in a human monocyte THP-1 cell line was evaluated by *** In this study,apharmacophore model constructed from a training set of TACE inhibitors was used to screen an in-house database of organic compounds,from which compound 1 emerged as a top *** a cell-free assay,compound 1inhibited TACE enzymatic activity in a dose-dependent ***,compound 1 inhibited the production of soluble TNF-αin human acute monocytic leukemia THP-1 cells without impacting nitric oxide production,and exhibited anti-proliferative activity against *** Compound 1 was found to inhibit TACE enzymatic activity in a cell-free system and LPS-induced TNF-αsecretion in *** envisage that compound 1 may be employed as a useful scaffold for the development of more potent TACE inhibitors.

关键词： pharmacophore TACE tumor necrosis factor virtual s

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